How much protein should we consume per day? What is the Recommended Daily Intake of protein, is it really enough and most importantly, what are the negative health effects of protein overconsumption?
Many arguments about protein consumption requirements and adequacy are based on the premise that the Recommended Daily Intake recommendations are accurate and that they are a target that the general population should aim for, as they represent a level beyond which no additional benefit can be observed.
But exactly how concrete are these arguments, and more importantly, what really is the protein target we should aim for to avoid health problems?
THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN
The Recommended Daily Allowance (RDA) represents the estimated average requirement plus 2 standard deviations, i.e. it is intended to cover minimum protein needs for 97.5% of the healthy population, with protein needs being based on defining the safe upper limits.
This meta-analysis used 58 nitrogen balance studies in adults for the purpose of estimating the protein requirement of healthy adults, of which, the analysis for determining the Recommended Daily Allowance was finally restricted to 19 studies.
A simple linear regression model was employed to identify the point of zero balance. Use of this approach resulted in an Estimated Average Requirement (EAR) and Recommended Daily Allowance of 0.66g and 0.83g protein/kg body weight/day, respectively, for adults.
The Recommended Daily Allowance rounded down to 0.8 g/kg body weight/day was utilized by the U.S. Institute of Medicine to derive the Dietary Reference Intakes (DRI) for protein in 2005 and for the recommendations of the WHO/FAO report on protein and amino acid intake recommendations in 2007.
THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN IS BASED ON INCORRECT ANALYSIS
Research on lysine requirements has demonstrated that the relationship between lysine intake and nitrogen balance is curvilinear, as the efficiency of protein utilization decreases as zero nitrogen balance is neared, which means that statistical models need to account for this nonlinearity.
A re-analysis of the published nitrogen balance data using the more appropriate, biphase linear regression model, resulted in a mean requirement of 0.91g protein per kg body weight per day and and a population-safe requirement estimate of 0.99g protein per kg body weight per day.
Thus, the use of the two-phase regression analysis results in protein requirement estimates that are close to 25% higher than when simple linear regression is applied.
THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN HAS BEEN CALCULATED USING OUTDATED METHODS
Even though the nitrogen balance technique is not a tracer method, it has been considered the gold standard for close to 100 years and is the basis for current nutritional guidelines.
However, even though the nitrogen balance method can a useful tool, it is not without its difficulties and limitations.
The theory underlying the nitrogen balance method proposes that the amount of nitrogen consumption required to balance the amount of nitrogen lost from the body represents the amount of dietary nitrogen intake needed to maintain lean body mass.
Nitrogen balance analysis conventionally uses urinary nitrogen excretion to represent nitrogen loss from the body, but nitrogen can be lost by other routes, including feces, sweat and wound exudates, which means that errors toward positive nitrogen balance due to overestimation of dietary nitrogen intake and underestimation of nitrogen losses from the body are highly likely when using this method, as the net result leads to an overly positive balance and therefore an underestimation of the requirement.
The above has led to nitrogen balance studies in adults consistently displaying positive balances, with considerable apparent retention of nitrogen, which is biologically implausible.
The evidence on whole-body protein turnover strongly suggests that the components of protein turnover (breakdown and synthesis), including amino acid oxidation, are influenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role.
In other words, dietary energy and carbohydrate intake can alter the utilization of amino acids for energy which in turn means that nitrogen balance can also be affected by these factors.
Evidence of alternative roles of amino acids beyond their role as subunits of protein synthesis, as for instance in neurotransmission, indicate that a competitive scenario for the available amino acid pool could likely impact the homeostasis measured in a nitrogen balance study.
The above limitations are further supported by studies that have shown that the nitrogen balance is not equivalent to amino acid balance.
Finally, there are considerations that render nitrogen balance impractical. Long periods of adaptation are required to equilibrate the body’s nitrogen pool: a minimum of 3 days is needed per level of test intake and 7–10 days of adaptation are needed to each intake of protein or amino acid.
These considerations have led to alternative approaches to understanding protein needs.
BETTER METHODS AND APPROACHES IN UNDERSTANDING PROTEIN NEEDS
In the latest US Institute of Medicine Dietary Reference Intakes for protein as well as in the WHO/FAO report on protein and amino acid intake recommendations, it is acknowledged that, when performed over a 24-hour period for estimating amino acid requirements, the indicator amino acid oxidation approach is probably the most satisfactory method on theoretical grounds, representing the current state of the art, and that it is the chosen method for estimated amino acid requirements where data are available.
The indicator amino acid oxidation method is based on the premise that when one indispensible amino acid is deficient, all other amino acids (including a tracer-labeled indicator amino acid) will be oxidized. As the intake of the deficient or limiting amino acid increases, the rate of oxidation of the other amino acids will decline as more amino acids are incorporated into protein.
Even though the indicator amino acid method is not without its own flaws, it would at least be interesting to see what the Recommended Daily Allowance would be if this method were to be employed instead of the nitrogen balance method, since the former addresses many of the limitations of the latter.
THE RECOMMENDED DAILY ALLOWANCE FOR PROTEIN USING BETTER METHODS
In the same study that performed the reanalysis of the published nitrogen balance data using two-phase regression analysis, the authors also used the indicator amino acid technique to determine protein requirements in healthy adults.
These values are approximately 1.5 times higher than the corresponding values published in the latest US Institute of Medicine Dietary Reference Intakes for protein and the WHO/FAO report on protein and amino acid intake recommendations.
Confirming the above, a recent study was conducted in young Chinese women using intact protein and meal feeding which applied the indicator amino acid oxidation method to determine protein requirements.
The results obtained for mean and population safe protein requirement were 0.91g and 1.09g per kg body weight per day, which are comparable to the estimates in the aforementioned study that used the indicator amino acid oxidation method.
RECOMMENDED DAILY INTAKE DOES NOT MEAN OPTIMAL INTAKE
Although the indicator amino acid oxidation method addresses many of the limitations of nitrogen balance, it still targets amino acid oxidation as an undesired metabolic outcome. Not only there is no evidence that efficiency equates to optimum metabolic health for adults, desirable metabolic outcomes can be expected as a result of amino acids being consumed in amounts greater than the requirements predicted from the nitrogen balance or indicator amino acid methods.
Dietary guidelines based solely on the efficiency of amino acid use for growth or nitrogen balance outcomes may be neglecting the fact that changes in intracellular amino acid concentrations and oxidative catabolism are an important means to regulate and support many normal metabolic responses beyond the synthesis of nitrogen-containing compounds.
Furthermore, research suggests that there may be a distinction between the minimal protein requirement (i.e. the Recommended Daily Allowance) and what is optimal to ensure long-term health, including the prevention of sarcopenia.
POPULATION GROUPS WITH HIGHER PROTEIN NEEDS
Even though both the US Institute of Medicine's latest Dietary Reference Intakes for protein and the WHO/FAO report on protein and amino acid intake recommendations do acknowledge special considerations for certain populations, the Recommended Daily Allowance is often considered a blanket statement and these considerations are overlooked.
New studies support increased needs for both total protein and certain amino acids for certain populations.
Populations whose protein needs are impacted by special metabolic demands include the older adults, young children, physically active adults, athletes in strength sports and athletes in endurance sports, pregnant and lactating women and individuals recovering from severe illness or trauma.
THE NEGATIVE EFFECTS OF PROTEIN ON HEALTH
But for the sake of argument, let's examine what theory suggests.
In a investigation of the fate of protein nitrogen, scientists were able to quantify the temporary accumulation of urea in body water during the peak rate of urea excretion and the amount hydrolysed in the gastrointestinal tract. An algorithm was then developed to estimate the liver's ability to amino acid amino acid aminogenesis and urea production, called the maximum rate of urea synthesis.
They found that the maximum rate of urea excretion in healthy subjects was 55 mg urea N per hour per kg3/4, which is achieved at an intake level of 0.53g of protein N per hour per kg3/4, while at higher protein intakes there is no further increase in urea excretion rate, but a prolongation of the duration of maximal rate of urea excretion, often in excess of 24 hours.
In the study, the maximum urea excretion rate averaged 65 mg urea N per hour per kg3/4 (with a range of 55 to 76) in healthy individuals, suggesting that the level of dietary protein that can be deaminated and processed through to urea by the liver in a 24 hour period is dependent on body weight and individual variation in efficiency of the process.
An 80 kg individual, for instance, could deaminate up to 301 g protein per day, but may be limited to 221 g protein per day, given the range in maximal rate of urea excretion determined by these data.
However, the safe intake level of protein consumption should actually be slightly higher than these figures, as not all protein is deaminated and converted to urea.
In other words, the protein that is used directly for structural/functional purposes, including bone and soft tissue growth, maintenance and repair plus production of hormones, antibodies, and enzymes, (i.e. the Recommended Daily Allowance) does not require deamination.
Therefore, adding our protein requirements to the level of protein that can be converted to urea, yields a theoretical maximal daily protein intake based on body weight and efficiency of urea synthesis in individuals.
An 80 kg individual, for example, could theoretically tolerate 325 g protein per day (range 285 to 365 g) without showing symptoms of hyperammonemia and hyperaminoacidemia considering the Recommended Daily Allowance from nitrogen balance (as 0.8g of protein per kg of body weight per day yields 64g/day for an 80 kg person).
On the other hand, this same 80 kg individual, could theoretically tolerate 357g protein per day (range 317 to 397g) without showing symptoms of hyperammonemia and hyperaminoacidemia considering the Recommended Daily Allowance, as calculated by studies using the indicator amino acid oxidation method (1.2g protein per kg body weight per day yields 96g/day for an 80 kg person).
Taking our theoretical approach one step further, it should be noted that it may be wise to interpret these approximations with caution, since the rate of amino acid absorption from protein is usually quite slow when compared to that of other macronutrients.
For instance, whey isolate, which is considered to be one of the “fastest” known proteins, has an absorption rate of ~8-10 hours per gram, while the protein from cooked eggs needs about ~2.8 hours per gram to absorb. In comparison, 357g of protein would need an absorption rate of approximately 15 g/hour in order to be absorbed in one day.
Moving from theory to practice, the same institution that provided the Recommended Daily Allowance, the US Institute of Medicine, defines the Acceptable Macronutrient Distribution Range (AMDR) for protein to be 10% to 35% of total energy for adults.
Consequently, for an 80kg individual who requires 2600kcal of energy per day, the Acceptable Macronutrient Distribution Range for protein intake ranges anywhere from 0.8125g to 2.84375g/kg body weight/day for adults (that is, well above the Recommended Daily Allowance), or from 65g to 227.5g per day.
- The Recommended Daily Allowance is based on an outdated method with many shortcomings and uses an improper methodology to analyze the available data.
- More recent methods suggest that the Recommended Daily Allowance needs to be around 1.2g per kg of bodyweight per day.
- The Recommended Daily Allowance is intended to cover minimum protein needs for 97.5% of the healthy population and minimum does not necessarily mean optimal.
- Special populations such as older adults, young children, physically active adults, strength and endurance athletes, pregnant and lactating women, and individuals recovering from severe illness or trauma probably require even more protein.
- Increasing protein intakes well above the Recommended Daily Allowance can be safe, without leading to negative effects in healthy humans in theory or practice, and the range of protein recommendations from health authorities is quite wide.
-Suprastratum: The authority on health, fitness and nutrition
- Rand WM, Pellett PL, Young VR. meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr. 2003 Jan;77(1):109-27. doi: 10.1093/ajcn/77.1.109. PMID: 12499330.
- Trumbo P, Schlicker S, Yates AA, Poos M; Food, Nutrition Board of the Institute of Medicine The National Academies (TNA). Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 2002;102(11): 1621-30.
- Joint FAO/WHO/UNU Expert Consultation on Protein and Amino Acid Requirements in Human Nutrition. Protein and amino acid requirements in human nutrition. World Health Organ Tech Rep Ser 2007;935:1-265.
- Millward DJ. Metabolic demands for amino acids and the human dietary requirement: Millward and Rivers (1988) revisited. J Nutr. 1998 Dec;128(12 Suppl):2563S-2576S. doi: 10.1093/jn/128.12.2563S. PMID: 9868206.
- Waterlow JC. the mysteries of nitrogen balance. nutr Res Rev. 1999 Jun;12(1):25-54. doi: 10.1079/095442299108728857. PMID: 19087445.
- Young VR, Taylor YS, Rand WM, Rand WM, Scrimshaw NS. protein requirements of man: efficiency of egg protein utilization at maintenance and submaintenance levels in young men. J Nutr. 1973 Aug;103(8):1164-74. doi: 10.1093/jn/103.8.1164. PMID: 4719728.
- Rand WM, Young VR. Statistical analysis of nitrogen balance data with reference to the lysine requirement in adults. J Nutr. 1999 Oct;129(10):1920-6. doi: 10.1093/jn/129.10.1920. doi: 10.1093/jn/129.10.1920. PMID: 10498769.
- Humayun MA, Elango R, Ball RO, Pencharz PB. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. Am J Clin Nutr. 2007 Oct;86(4):995-1002. doi: 10.1093/ajcn/86.4.995. PMID: 17921376.
- Elango R, Humayun MA, Ball RO, Pencharz PB. evidence that protein requirements have been significantly underestimated. curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):52-7. doi: 10.1097/MCO.0b013e328332f9b7. PMID: 19841581.
- Wolfe RR, Kim IY, Park S, Ferrando A. Tracing metabolic flux to assess optimal dietary protein and amino acid consumption. Exp Mol Med. 2022 Sep;54(9):1323-1331. doi: 10.1038/s12276-022-00817-w. Epub 2022 Sep 8. PMID: 36075948; PMCID: PMC9534933.
- Waterlow JC. the mysteries of nitrogen balance. nutr Res Rev. 1999 Jun;12(1):25-54. doi: 10.1079/095442299108728857. PMID: 19087445.
- Dalangin R, Kim A, Campbell RE. The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection. int J Mol Sci. 2020 Aug 27;21(17):6197. doi: 10.3390/ijms21176197. PMID: 32867295; PMCID: PMC7503967.
- Fuller MF, Garlick PJ. Human amino acid requirements: can the controversy be resolved? Annu Rev Nutr. 1994;14:217-41. doi: 10.1146/annurev.nu.14.070194.001245. PMID: 7946519.
- Pencharz PB, Elango R, Wolfe RR. Recent developments in understanding protein needs - How much and what kind should we eat? Appl Physiol Nutr Metab. 2016 May;41(5):577-80. doi: 10.1139/apnm-2015-0549. epub 2016 Apr 25. PMID: 27109436.
- Weiler M, Hertzler SR, Dvoretskiy S. Is It Time to Reconsider the U.S. Recommendations for Dietary Protein and Amino Acid Intake? Nutrients. 2023 Feb 6;15(4):838. doi: 10.3390/nu15040838. PMID: 36839196; PMCID: PMC9963165.
- Elango R, Ball RO, Pencharz PB. indicator amino acid oxidation: concept and application. J Nutr. 2008 Feb;138(2):243-6. doi: 10.1093/jn/138.2.243. PMID: 18203885.
- Elango R, Ball RO, Pencharz PB. recent advances in determining protein and amino acid requirements in humans. br j nutr. 2012 Aug;108 Suppl 2:S22-30. doi: 10.1017/S0007117114512002504. PMID: 23107531.
- Tian Y, Liu J, Zhang Y, Piao J, Gou L, Tian Y, Li M, Ji Y, Yang X. Examination of Chinese habitual dietary protein requirements of Chinese young female adults by indicator amino acid method. Asia Pac J Clin Nutr. 2011;20(3):390-6. PMID: 21859657.
- Layman DK, Anthony TG, Rasmussen BB, Adams SH, Lynch CJ, Brinkworth GD, Davis TA. defining meal requirements for protein to optimize metabolic roles of amino acids. Am J Clin Nutr. 2015 Jun;101(6):1330S-1338S. doi: 10.3945/ajcn.114.084053. doi: 10.3945/ajcn.114.084053. Epub 2015 Apr 29. PMID: 25926513;. PMCID: PMC5278948.
- Wolfe RR, Miller SL, Miller SL, Miller KB. optimal protein intake in the elderly. clin Nutr. 2008 Oct;27(5):675-84. doi: 10.1016/j.clnu.2008.06.008. epub 2008 Sep 25. PMID: 18819733.
- Baum JI, Kim IY, Wolfe RR. Protein Consumption and the Elderly: What Is the Optimal Level of Intake? Nutrients. 2016 Jun 8;8(6):359. doi: 10.3390/nu8060359. PMID: 27338461; PMCID: PMC4924200.
- Phillips SM, Chevalier S, Leidy HJ. Protein "requirements" beyond the RDA: implications for optimizing health. appl Physiol Nutr Metab. 2016 May;41(5):565-72. doi: 10.1139/apnm-2015-0550. epub 2016 Feb 9. erratum in: appl Physiol Nutr Metab. 2022 May;47(5):615. PMID: 26960445.
- Phillips SM, Chevalier S, Leidy HJ. correction: protein "requirements" beyond the RDA: implications for optimizing health. appl Physiol Nutr Metab. 2022 May;47(5):615. doi: 10.1139/apnm-2022-0131. epub 2022 Mar 29. erratum for: appl Physiol Nutr Metab. 2016 May;41(5):565-72. PMID: 35349368.
- Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, Phillips S, Sieber C, Stehle P, Teta D, Visvanathan R, Volpi E, Boirie Y. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013 Aug;14(8):542-59. doi: 10.1016/j.jamda.2013.05.021. epub 2013 Jul 16. PMID: 23867520.
- Paddon-Jones D, Campbell WW, Campbell WW, Jacques PF, Kritchevsky SB, Moore LL, Rodriguez NR, van Loon LJ. protein and healthy aging. am j clin nutr. 2015 Jun;101(6):1339S-1345S. doi: 10.3945/ajcn.114.084061. epub 2015 Apr 29. pmid: 25926511.
- Volpi E, Campbell WW, Dwyer JT, Johnson MA, Jensen GL, Morley JE, Wolfe RR. Is the optimal level of protein intake for older adults greater than the recommended dietary allowance? J Gerontol A Biol Sci Med Sci. 2013 Jun;68(6):677-81. doi: 10.1093/gerona/gls229. epub 2012 Nov 26. PMID: 23183903; PMCID: PMC3660117.
- Rafii M, Chapman K, Elango R, Campbell WW, Ball RO, Pencharz PB, Courtney-Martin G. Dietary Protein Requirement of Men >65 Years Old Determined by the Indicator Amino Acid Oxidation Technique Is Higher than the Current Estimated Average Requirement. J Nutr. 2015 Apr 1;146(4):681-687. doi: 10.3945/jn.115.225631. PMID: 26962173.
- Rafii M, Chapman K, Owens J, Elango R, Campbell WW, Campbell WW, Ball RO, Pencharz PB, Courtney-Martin G. Dietary protein requirement of female adults >65 years determined by the indicator amino acid oxidation technique is higher than current recommendations. J Nutr. 2015 Jan;145(1):18-24. doi: 10.3945/jn.114.197517. epub 2014 Oct 15. PMID: 25320185.
- Tang M, McCabe GP, Elango R, Pencharz PB, Ball RO, Campbell WW. assessment of protein requirement in octogenarian women with use of the indicator amino acid oxidation technique. Am J Clin Nutr. 2014 Apr;99(4):891-8. doi: 10.3945/ajcn.112.042325. epub 2014 Jan 15. PMID: 24429540; PMCID: PMC3953883.
- Elango R, Humayun MA, Ball RO, Pencharz PB. protein requirement of healthy school-age children determined by the indicator amino acid oxidation method. Am J Clin Nutr. 2011 Dec;94(6):1545-52. doi: 10.3945/ajcn.111.012815. epub 2011 Nov 2. PMID: 22049165.
- Hunter R, Kerksick CM, Campbell BI, Cribb PJ, Wells SD, Skwiat TM, Purpura M, Ziegenfuss TN, Ferrando AA, Arent SM, Smith-Ryan AE, Stout JR, Arciero PJ, Ormsbee MJ, Taylor LW, Wilborn CD, Kalman DS, Kreider RB, Willoughby DS, Hoffman JR, Krzykowski JL, Antonio J. International Society of Sports Nutrition Position Stand: protein and exercise. J Int Soc Sports Nutr. 2017 Jun 20;14:20. doi: 10.1186/s12970-017-0177-8. PMID: 28642676; PMCID: PMC5477153.
- Bandegan A, Courtney-Martin G, Rafii M, Pencharz PB, Lemon PW. Indicator Amino Acid-Derived Estimate of Dietary Protein Requirement for Male Bodybuilders on a Nontraining Day Is Several-Fold Greater than the Current Recommended Dietary Allowance. J Nutr. 2017 May;147(5):850-857. doi: 10.3945/jn.116.236331. epub 2017 Feb 8. PMID: 28179492.
- Malowany JM, West DWD, Williamson E, Volterman KA, Abou Sawan S, Mazzulla M, Moore DR. protein to Maximize Whole-Body Anabolism in Resistance-trained Females after Exercise. med sci sports exerc. 2019 Apr;51(4):798-804. doi: 10.1249/MSS.0000000000001832. PMID: 30395050. doi: 10.1249/MSS.000000001832. PMID: 30395050.
- Bandegan A, Courtney-Martin G, Rafii M, Pencharz PB, Lemon PWR. Indicator amino acid oxidation protein requirement estimate in endurance-trained men 24 h postexercise exceeds both the EAR and current athlete guidelines. Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E741-E748. doi: 10.1152/ajpendo.00174.2018. epub 2019 Feb 19. PMID: 30779631.
- Kato H, Suzuki K, Bannai M, Moore DR. Protein Requirements Are Elevated in Endurance Athletes after Exercise as Determined by the Indicator Amino Acid Oxidation Method. PLoS One. 2016 Jun 20;11(6):e0157406. doi: 10.1371/journal.pone.0157406. PMID: 27322029; PMCID: PMC4913918.(Stephens et al. 2015).
- Stephens TV, Payne M, Ball RO, Pencharz PB, Elango R. Protein requirements of healthy pregnant women during early and late gestation are higher than current recommendations. J Nutr. 2015 Jan;145(1):73-8. doi: 10.3945/jn.114.198622. epub 2014 Sep 24. PMID: 25527661.
- Rasmussen B, Ennis M, Pencharz P, Ball R, Courtney-martin G, Elango R. Protein Requirements of Healthy Lactating Women Are Higher Than the Current Recommendations. current Developments in Nutrition. 2020 May 29;4(Supplement_2):653-3. doi: 10.1093/cdn/nzaa049_046
- Rudman D, DiFulco TJ, Galambos JT, Smith RB 3rd, Salam AA, Warren WD. Maximum rates of excretion and synthesis of urea in normal and cirrhotic subjects. J Clin Invest. 1973 Sep;52(9):2241-9. doi: 10.1172/JCI107410. PMID: 4727456; PMCID: PMC333026.
- Bilsborough S, Mann N. A review of issues of dietary protein intake in humans. Int J Sport Nutr Exerc Metab. 2006 Apr;16(2):129-52. doi: 10.1123/ijsnem.16.2.129. PMID: 16779921.
- Millward DJ. Identifying recommended dietary allowances for protein and amino acids: a critique of the 2007 WHO/FAO/UNU report. Br J Nutr. 2012 Aug;108 Suppl 2:S3-21. doi: 10.1017/S000711114512002450. PMID: 23107542.
- Matsumoto M, Narumi-Hyakutake A, Kakutani Y, Tsuji M, Hatamoto Y, Higaki Y, Sasaki S. Evaluation of protein requirements using the indicator amino acid oxidation method: a scoping review. J Nutr. 2023 Aug 10:S0022-3166(23)72529-7. doi: 10.1016/j.tjnut.2023.07.015. epub ahead of print. PMID: 37573015.